A 68-year-old man comes to the office for follow-up. The patient has a 10-year history of end-stage renal disease due to diabetic and hypertensive nephropathy and receives intermittent hemodialysis. Current medications are losartan, metoprolol, amlodipine, short- and long-acting insulins, and epoetin alpha. His calcium acetate and calcitriol therapy were stopped 3 months ago due to an elevated serum calcium level. The patient is adherent with medications and dietary restrictions. Laboratory results are as follows: Which of the following is the most likely underlying cause of this patient's elevated serum calcium level?

Question

A 68-year-old man comes to the office for follow-up.  The patient has a 10-year history of end-stage renal disease due to diabetic and hypertensive nephropathy and receives intermittent hemodialysis.  Current medications are losartan, metoprolol, amlodipine, short- and long-acting insulins, and epoetin alpha.  His calcium acetate and calcitriol therapy were stopped 3 months ago due to an elevated serum calcium level.  The patient is adherent with medications and dietary restrictions.  Laboratory results are as follows:  Which of the following is the most likely underlying cause of this patient's elevated serum calcium level?

Quizplus · Accepted Answer

Explanation: 11ec25c8_d8cb_467d_bc81_a15eb5df7dcd_MD0003_00 Chronic kidney disease (CKD) is associated with hypocalcemia due to decreased renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (the more active form). Concurrently, decreased glomerular filtration leads to inadequate clearance of plasma phosphate. The resulting hypocalcemia and hyperphosphatemia stimulate secretion of parathyroid hormone (PTH), leading to high circulating PTH levels (ie, secondary hyperparathyroidism). secondary hyperparathyroidism In patients with long-standing CKD, especially those with end-stage renal disease (ESRD), chronic parathyroid stimulation can lead to parathyroid hyperplasia. This is associated with autonomous PTH secretion (ie, not suppressed by rising calcium levels) due to downregulation of calcium-sensing receptor and vitamin D receptor in the parathyroid glands. The net effect, termed tertiary hyperparathyroidism, is characterized by: Extremely high serum PTH levels Hypercalcemia due to mobilization from bone Hyperphosphatemia due to renal phosphate retention This patient has hypercalcemia despite discontinuation of calcium and calcitriol therapy. In the setting of ESRD, hyperphosphatemia, and a very high PTH level, this presentation is consistent with tertiary hyperparathyroidism. (Choice A) PTH is a peptide hormone that is metabolized primarily in the liver. Although a lesser amount is metabolized in the kidneys, intact renal function is not necessary for clearance of PTH. (Choice B) Humoral hypercalcemia of malignancy is characterized by ectopic production of PTH-related peptide and is a common cause of paraneoplastic hypercalcemia. Ectopic production of intact PTH is a very rare paraneoplastic syndrome and is not the cause of tertiary hyperparathyroidism in ESRD. (Choice D) Activation of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D is dependent on renal expression of 1-alpha-hydroxylase, which is decreased (not increased) in patients with CKD. Furthermore, excessive activation of vitamin D would suppress PTH production. (Choice E) Calcium circulates in a protein-bound fraction and a non-protein-bound ionized fraction. Pseudohypercalcemia refers to an elevated total serum calcium level due to excessive levels of serum proteins (eg, albumin, immunoglobulin) with a normal ionized calcium level. These patients are in a physiologically eucalcemic state with normal PTH levels. Educational objective: Patients with long-standing chronic kidney disease often have hypocalcemia and hyperphosphatemia, which can lead to chronic parathyroid stimulation. Over time, this can cause parathyroid hyperplasia and autonomous parathyroid hormone (PTH) secretion. The net effect, termed tertiary hyperparathyroidism, is characterized by hypercalcemia, hyperphosphatemia, and extremely high serum PTH levels. References: Secondary and tertiary hyperparathyroidism in chronic kidney disease: an endocrine and renal perspective. (http://www.ncbi.nlm.nih.gov/pubmed/31741895)

A 68-Year-Old Man Comes to the Office for Follow-Up